Mice differ from one another in their susceptibility to retroviruses and retrovirus-induced diseases. These differences are due to various mouse chromosomal genes, and we have been engaged in an ongoing effort to characterize mouse genes involved in this resistance, and to identify the viral targets of resistance. In one series of experiments, we have been working on a variant mouse mammary tumor virus (MMTV) which induces T- cell lymphoma. These tumors contain novel MMTV integrations and we are in the process of identifying cellular genes at these sites. Of the 4 integrations examined to date, 3 of these map to regions not implicated in lymphomagenesis by the leukemia viruses, but the fourth maps near c-myc, a protooncogene clearly involved in tumor induction by leukemia viruses (Dudley, Adamson). We continued to investigate the viral resistance gene, Rmcf, which is responsible for resistance to the polytropic class of leukemia viruses. We have transferred this resistance to a wild mouse genetic background by serial backcrossing and used these partial congenics to identify a tightly linked chromosomally integrated copy of the viral envelope. This viral envelope is a candidate for resistance that may function by blocking cell surface viral receptors. We are working on the cloning this gene (Lyu, Lee). We have initiated studies on a serum factor found in most mice which inactivates leukemia viruses. We have shown that this factor does not inactivate viruses of the ecotropic and amphotropic host range groups, but that it strongly inactivates polytropic viruses and, less strongly, xenotropic viruses. We have determined that the presence of this factor is under single gene control and we have initiated a genome scan to identify the responsible locus (Lee). The wild mouse species M. castaneus differs from inbred strains in that these mice are resistant to polytropic viruses. This resistance is most likely due to the presence of an altered version of the cell surface receptor. Genetic crosses now suggest that additional genes in the wild mouse genetic background may contribute to this resistance, and we are in the process of analyzing additional genetic crosses to identify the number and chromosomal distribution of these genes (Lee).